Recent advances in TRPV4 agonists and antagonists

Brian G Lawhorn; Edward J Brnardic; David J Behm

doi:10.1016/j.bmcl.2020.127022

Recent advances in TRPV4 agonists and antagonists

Bioorg Med Chem Lett. 2020 Apr 15;30(8):127022. doi: 10.1016/j.bmcl.2020.127022. Epub 2020 Feb 8.

Authors

Brian G Lawhorn¹, Edward J Brnardic², David J Behm²

Affiliations

¹ Medicinal Chemistry, Medicine Design, and Early Development Leaders, Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, United States. Electronic address: brian.2.lawhorn@gsk.com.
² Medicinal Chemistry, Medicine Design, and Early Development Leaders, Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, United States.

PMID: 32063431
DOI: 10.1016/j.bmcl.2020.127022

Abstract

TRPV4 is a ubiquitously expressed, non-selective cation channel activated by a range of stimuli including hypotonicity, temperature, pH, stretch and endogenous ligands. Agents that modulate TRPV4 are sought as potential therapeutics for the treatment of many diseases including osteoarthritis, respiratory illnesses, gastrointestinal disorders, pain and congestive heart failure. In recent years, significant advances in TRPV4 drug discovery have been realized as at least seven novel TRPV4 agonist or antagonist templates were reported and the first selective TRPV4 antagonist was evaluated in early clinical trials.

Keywords: Clinical candidate; Lead optimization; TRPV4 agonist; TRPV4 antagonist.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Biological Products / chemistry
Biological Products / pharmacology*
Drug Discovery
Humans
Models, Molecular
Molecular Structure
Phorbols / chemistry
Phorbols / pharmacology*
TRPV Cation Channels / agonists*
TRPV Cation Channels / antagonists & inhibitors*

Substances

Biological Products
Phorbols
TRPV Cation Channels
TRPV4 protein, human
phorbol